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dc.contributor.author
Hasgall, Philippe A.
dc.contributor.author
Hoogewijs, David
dc.contributor.author
Faza, Marius B.
dc.contributor.author
Panse, Vikram G.
dc.contributor.author
Wenger, Roland H.
dc.contributor.author
Camenisch, Gieri
dc.date.accessioned
2018-09-20T11:05:55Z
dc.date.available
2017-06-09T13:17:42Z
dc.date.available
2018-09-20T11:05:55Z
dc.date.issued
2011-07-13
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0022107
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/38733
dc.identifier.doi
10.3929/ethz-b-000038733
dc.description.abstract
The hypoxia–inducible transcription factor (HIF) is a key component of the cellular adaptation mechanisms to hypoxic conditions. HIFα subunits are degraded by prolyl-4-hydroxylase domain (PHD) enzyme-dependent prolyl-4-hydroxylation of LxxLAP motifs that confer oxygen-dependent proteolytic degradation. Interestingly, only three non-HIFα proteins contain two conserved LxxLAP motifs, including the putative RNA helicase with a zinc finger domain HELZ. However, HELZ proteolytic regulation was found to be oxygen-independent, supporting the notion that a LxxLAP sequence motif alone is not sufficient for oxygen-dependent protein destruction. Since biochemical pathways involving RNA often require RNA helicases to modulate RNA structure and activity, we used luciferase reporter gene constructs and metabolic labeling to demonstrate that HELZ overexpression activates global protein translation whereas RNA-interference mediated HELZ suppression had the opposite effect. Although HELZ interacted with the poly(A)-binding protein (PABP) via its PAM2 motif, PABP was dispensable for HELZ function in protein translation. Importantly, downregulation of HELZ reduced translational initiation, resulting in the disassembly of polysomes, in a reduction of cell proliferation and hypophosphorylation of ribosomal protein S6.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.title
The Putative RNA Helicase HELZ Promotes Cell Proliferation, Translation Initiation and Ribosomal Protein S6 Phosphorylation
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
ethz.journal.title
PLoS ONE
ethz.journal.volume
6
en_US
ethz.journal.issue
7
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e22107
en_US
ethz.size
11 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
006206116
ethz.publication.place
Lawrence, KS, USA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich, direkt::00012 - Lehre und Forschung, direkt::00007 - Departemente, direkt::02030 - Departement Biologie / Department of Biology::02517 - Institut für Biochemie (IBC) / Institute of Biochemistry (IBC)::03884 - Panse, Vikram G. (SNF-Professur) (ehemalig)
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich, direkt::00012 - Lehre und Forschung, direkt::00007 - Departemente, direkt::02030 - Departement Biologie / Department of Biology::02517 - Institut für Biochemie (IBC) / Institute of Biochemistry (IBC)::03884 - Panse, Vikram G. (SNF-Professur) (ehemalig)
ethz.date.deposited
2017-06-09T13:18:04Z
ethz.source
ECIT
ethz.identifier.importid
imp59364e540c3d360323
ethz.ecitpid
pub:62393
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-12T10:58:20Z
ethz.rosetta.lastUpdated
2018-09-20T11:05:58Z
ethz.rosetta.versionExported
true
ethz.COinS
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